Macrolides are a well-known family of antimicrobial agents. Erythromycin A, a 14-membered macrolide, was isolated in 1952 from Streptomyces erythreus. Examples of macrolides being used as therapeutic agents are roxithromycin, clarithromycin and azithromycin (azalide). Ketolides are semisynthetic 14-membered ring macrolide derivatives, characterized by the presence of a keto function at position 3 instead of L-cladinose moiety present in the macrolactone ring. Telithromycin and Cethromycin are examples of ketolides.
U.S. Pat. No. 4,331,803 discloses 6-O-methyl derivative of erythromycin i.e. Clarithromycin. U.S. Pat. No. 4,349,545 discloses Roxithromycin. The azalide Azithromycin is disclosed in U.S. Pat. No. 4,517,359. Telithromycin is described in EP Patent 680967A1 and corresponding U.S. Pat. No. 5,635,485 and Bioorg. Med. Chem. Lett. 1999, 9(21), 3075-3080. Another ketolide Cethromycin (ABT773) is disclosed in WO 98/09978, and J. Med. Chem., 2000, 43, 1045.
In view of the wide use of the macrolide and ketolide compounds as broad-spectrum antimicrobial compounds, there is immense interest in developing these compounds. As can be seen, these compounds are complex chemical compounds with several asymmetric centers, which make their synthesis and purification a difficult task. The present inventors have now surprisingly found an efficient method for synthesizing these compounds in better yields and purity.